Effect of Combined Alcohol and E-Cigarette Use on Blood Brain Barrier

(Philadelphia, PA) – With a variety of flavors and widespread perceptions of safety, e-cigarettes appeal to an array of users and especially to adolescents. E-cigarette use, however, is linked to increased alcohol consumption, as well as the use of other substances and drugs. The health effects of such combinations remain almost entirely unknown.

Now, with new funding from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the National Institutes of Health (NIH), researchers at the Lewis Katz School of Medicine at Temple University hope to cast light on the impact of combined alcohol and e-cigarette use on the blood brain barrier – the cell layer that regulates the passage of substances into the sensitive tissues of the central nervous system.

The new grant provides principal investigator Yuri Persidsky, MD, PhD, Chair of the Department of Pathology and Laboratory Medicine at the Lewis Katz School of Medicine, and colleagues with more than half a million dollars in funding annually for the next five years.

“Clinical studies in human volunteers suggest that e-cigarettes alone negatively impact microvessels in the brain and increase levels of inflammatory factors in the blood,” Dr. Persidsky explained. “With our new funding from the NIAAA, we plan to identify and better understand the factors and mechanisms behind these events, which could have adverse effects on brain function.”

The blood brain barrier normally is highly selective, allowing only some molecules to enter the central nervous system and preventing the entry of many others. When it is damaged or impaired, however, this protective function breaks down. As molecules that are typically kept out – such as immune cells, inflammatory proteins, and toxins – make their way across the barrier and into the brain, they fuel inflammatory processes that damage neurons and contribute to cognitive decline and decreased neurological function.

Previous studies have shown that e-cigarette use alone can disrupt blood brain barrier function and can cause inflammation in the brain. In animals, exposure to e-cigarette vapors is linked to a decrease in factors that support neuronal function and to increases in the generation of reactive oxygen species (ROS) and the accumulation of inflammatory molecules in endothelial cells. Increases in such factors, especially ROS, are known to hinder the function of mitochondria, the tiny batteries inside cells that produce energy to fuel virtually all cellular functions.

Thanks to the new grant, Dr. Persidsky and colleagues can now specifically investigate the new mechanism of injury of alcohol and e-cigarettes and the impact of elevated levels of proinflammatory molecules, including ROS, on the function of mitochondria in the endothelial cells of the blood brain barrier. Their experiments will be carried out using both in vitro systems and animal models that combine the effects of chronic alcohol use and e-cigarette inhalation. Preliminary data collected from these models has already indicated that combined alcohol and e-cigarette exposure leads to enhanced mitochondrial dysfunction and cognitive demise.

As the researchers elucidate mechanisms of endothelial and blood brain barrier damage involving mitochondria, they hope to also identify biomarkers for possible clinical use. “The discovery of biomarkers associated with alcohol and e-cigarette exposure that can be measured in the blood could lead to the development of future screening strategies to detect and assess levels of blood brain barrier injury in individuals who use these substances,” Dr. Persidsky added.

Research reported in this publication was supported by the National Institute On Alcohol Abuse And Alcoholism of the National Institutes of Health, award number 1R01AA030841-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About the Lewis Katz School of Medicine

Founded in 1901, the Lewis Katz School of Medicine at Temple University attracts students and faculty committed to advancing individual and population health through culturally competent patient care, research, education, and service. The School confers the MD degree; MS and PhD degrees in Biomedical Science; the MA in Urban Bioethics; the MS in Physician Assistant studies; a certificate in Narrative Medicine; a non-degree post-baccalaureate program; several dual degree programs with other Temple University schools; continuing medical education programs; and in partnership with Temple University Hospital, 40 residency and fellowship programs for physicians. The School also manages a robust portfolio of publicly and privately funded transdisciplinary studies aimed at advancing the prevention, diagnosis, and treatment of disease -- with specialized research centers focused on heart disease, cancer, substance use disorder, metabolic disease, and other regional and national health priorities. To learn more about the Lewis Katz School of Medicine, please visit: medicine.temple.edu.